ANAVEX3-71 for Schizophrenia
(SZ-001 Trial)
Recruiting in Palo Alto (17 mi)
Age: 18 - 65
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Anavex Life Sciences Corp.
Must be taking: Atypical antipsychotics
Must not be taking: Clozapine, Daytime quetiapine
Disqualifiers: Pregnancy, Suicidal risk, others
Prior Safety Data
Trial Summary
What is the purpose of this trial?A study to evaluate the safety, tolerability, efficacy, pharmacokinetics, and electrophysiology of ANAVEX3-71 in patients with Schizophrenia.
Will I have to stop taking my current medications?
You will need to stay on your current antipsychotic medications if they are second-generation types, except for clozapine, which is not allowed. You can use quetiapine for sleep at doses less than 300 mg, but not during the day.
How is the drug ANAVEX3-71 different from other schizophrenia treatments?
ANAVEX3-71 is unique because it targets alpha7-nicotinic acetylcholine receptors, which are often deficient in people with schizophrenia. This mechanism may help improve cognitive and sensory processing deficits associated with the condition, offering a novel approach compared to traditional antipsychotics.
12345Eligibility Criteria
Adults aged 18-50 with stable schizophrenia, on consistent antipsychotic medication for at least 6 weeks, and a BMI between 18.5 to 40 kg/m2 can join this trial. They must have a specific cognition score, not be drug or alcohol users, and agree to stay inpatient as required. Pregnant individuals or those with recent investigational drug use are excluded.Inclusion Criteria
Has a negative urine screen for drugs of abuse and negative alcohol breath test at screening and check-in
I have been diagnosed with schizophrenia for at least 1 year.
My schizophrenia symptoms have been stable for at least 6 weeks.
+9 more
Exclusion Criteria
Simpson Angus Scale (SAS) total score ≥5 at the screening and baseline visits
Risk for suicidal behavior during the study
I have not been diagnosed with a mental health disorder other than schizophrenia in the past year.
+8 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Part A: Multiple Ascending Dose
Participants receive multiple ascending doses of ANAVEX3-71 for dose selection, safety, and pharmacokinetics assessment
10 days
In-patient study
Part B: Double-Blind, Placebo-Controlled
Participants receive either ANAVEX3-71 or placebo to assess exploratory efficacy and continued repeat-dose safety
28 days
In-patient study
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Participant Groups
The study is testing ANAVEX3-71 oral capsules against placebo to assess their safety and effectiveness in treating schizophrenia symptoms. It also looks into how the body processes the drug and its effects on brain function.
5Treatment groups
Active Control
Placebo Group
Group I: ANAVEX3-71 30 mg TID (Part A)Active Control1 Intervention
The first active treatment arm of the study during Part A (multiple ascending doses).
Group II: ANAVEX3-71 60 mg TID (Part A)Active Control1 Intervention
The second active treatment arm of the study during Part A (multiple ascending doses).
Group III: ANAVEX3-71 TBD mg TID (Part B)Active Control1 Intervention
The active arm of Part B of the study. The dose will be determined based on data obtained in Part A.
Group IV: ANAVEXX3-71 Placebo TID (Part A)Placebo Group1 Intervention
The placebo arm of Part A (multiple ascending doses).
Group V: ANAVEX3-71 Placebo TID (Part B)Placebo Group1 Intervention
The placebo arm of Part B of the study.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
CenExel Hassman Research InstituteMarlton, NJ
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Who Is Running the Clinical Trial?
Anavex Life Sciences Corp.Lead Sponsor
Hassman Research InstituteCollaborator
Cognitive Research CorporationIndustry Sponsor
COGNISIONCollaborator
References
Effects of an alpha 7-nicotinic agonist on default network activity in schizophrenia. [2021]3-(2,4-dimethoxybenzylidene)-anabaseine (DMXB-A) is a partial agonist at α7 nicotinic acetylcholine receptors that has been evaluated clinically for treatment of schizophrenia. This study examined the effects of DMXB-A on default network activity as a biomarker for drug effects on pathologic brain function associated with schizophrenia.
DMXB, an alpha7 nicotinic agonist, normalizes auditory gating in isolation-reared rats. [2018]Impaired auditory gating is common in schizophrenic patients. Evidence suggests that this deficit is related to a reduced number of alpha(7) nicotinic receptors and therefore treatment with alpha(7) nicotinic agonists may improve this condition. 3-(2,4)-Dimethoxybenzylidine anabaseine (DMXB; also known as GTS-21) is such an agonist and has shown efficacy in mice both orally and intraperitoneally.
Functional magnetic resonance imaging of effects of a nicotinic agonist in schizophrenia. [2021]3-(2,4-Dimethoxybenzylidene)-anabaseine (DMXB-A) is a partial agonist at alpha7-nicotinic acetylcholine receptors and is now in early clinical development for treatment of deficits in neurocognition and sensory gating in schizophrenia. During its initial phase 2 test, functional magnetic resonance imaging (fMRI) studies were conducted to determine whether the drug had its intended effect on hippocampal inhibitory interneurons. Increased hemodynamic activity in the hippocampus in schizophrenia is found during many tasks, including smooth pursuit eye movements, and may reflect inhibitory dysfunction. Placebo and two doses of drug were administered in a random, double-blind crossover design. After the morning drug/placebo ingestion, subjects underwent fMRI while performing a smooth pursuit eye movement task. Data were analyzed from 16 nonsmoking patients, including 7 women and 9 men. The 150-mg dose of DMXB-A, compared with placebo, diminished the activity of the hippocampus during pursuit eye movements, but the 75-mg dose was ineffective. The effect at the 150-mg dose was negatively correlated with plasma drug levels. The findings are consistent with the previously established function of alpha7-nicotinic receptors on inhibitory interneurons in the hippocampus and with genetic evidence for deficits in these receptors in schizophrenia. Imaging of drug response is useful in planning future clinical tests of this compound and other nicotinic agonists for schizophrenia.
Anabasine, a selective nicotinic acetylcholine receptor agonist, antagonizes MK-801-elicited mouse popping behavior, an animal model of schizophrenia. [2013]The expression of the alpha7-nicotinic acetylcholine receptor is diminished in selected brain areas of patients with schizophrenia. This diminished expression may account for the pathophysiological deficits of sensory inhibition and smooth pursuit eye movement performance in these patients. Furthermore, the deficits in sensory inhibition and smooth pursuit eye movement performance in schizophrenia appear to be inherited in an autosomal dominant fashion; thus, the "alpha7-nicotinic acetylcholine receptor-deficiency" may be a necessary condition for expression of schizophrenia. This deficit has encouraged speculation about the possible therapeutic benefit of selective alpha7-nicotinic acetylcholine receptor agonist interventions in this disorder. In view of this, we sought to examine the effect of anabasine, a selective alpha7-nicotinic acetylcholine receptor agonist, on popping behavior in mice elicited by MK-801. MK-801, a high affinity analogue of phencyclidine (PCP), is a noncompetitive N-methyl-D-aspartic acid (NMDA) receptor antagonist that binds to the hydrophobic domain of this ligand-gated channel. PCP is known to precipitate a schizophreniform psychosis in susceptible individuals, causing productive (e.g. hallucinations) deficit (e.g. affective blunting, amotivation, and social withdrawal), cognitive and motor symptoms similar to those seen in naturally-occurring schizophrenia. Behaviors elicited by MK-801 in mice reflect a pharmacologically-induced state of NMDA receptor hypofunction (NRH), which has been proposed to exist in schizophrenia. Compounds that attenuate MK-801-elicited behaviors, which are identified in this animal model, may have the potential to treat schizophrenia, including deficit and cognitive symptoms. In the current study, anabasine attenuated MK-801-elicited popping at a dose that did not cause clonic seizures. The development of alpha7-nicotinic acetylcholine receptor agonist interventions for schizophrenia must consider their potential liability to elicit seizure activity.
Initial phase 2 trial of a nicotinic agonist in schizophrenia. [2022]Nicotinic acetylcholine receptors are possible therapeutic targets for schizophrenia, as shown by neurobiological and molecular evidence for deficiencies in expression of alpha(7)-nicotinic receptors. Patients' heavy smoking suggests attempted self-medication through this mechanism. The agent 3-(2,4-dimethoxybenzylidene) anabaseine (DMXB-A) is a partial alpha(7)-nicotinic agonist and can be taken orally. A phase 1 trial showed evidence for cognitive enhancement in schizophrenia.